The blood-brain barrier (BBB) can be divided into the endothelial barrier within the capillaries and the glial blood-cerebrospinal fluid barrier (BCSFB) located in the circumventricular organs and the choroid plexus. The barrier proper is formed by tight junctions. Whereas the astrocytes are suggested to play a role in the induction or maintenance of the endothelial BBB, this is not well defined for the glial BCSFB. The structure of BBB tight junctions (TJs) at best can be investigated by the freeze-fracturing method: the complexity of the network of BBB-TJ strands as well as the association of the TJ particles with the inner leaflet of the endothelial membrane (P-face) is unique among all endothelial cells in the body. However, cultivation of brain endothelial cells changes dramatically the structure of the TJs suggesting complex interactions between the endothelial cells and the brain microenvironment. In contrast, the choroid plexus tight junctions are morphologically characterized by parallel strands mainly associated to the P-face. The molecular components of TJs include occludin, members of the claudin family, and JAM and ESAM as transmembrane proteins, and ZO-1,-2,-3, cingulin and others as TJ associated proteins. In the BBB, occludin, claudin-3, claudin-5 and claudin-12 have been identified. The main TJ proteins in the choroid plexus are, besides occludin, claudin -1, claudin-2, claudin-3, and claudin-11. In human glioma, and in inflammatory diseases, loss of claudin-3 has been described. The results suggest an extremely interactive regulation of the BBB, in which glial cells, the extracellular matrix and the endothelial cells are involved.

Acknowledgements: 

The collaborations with and suggestions of Ingolf Blasig and Jörg Piontek (Berlin-Buch), Stefan Liebner (Frankfurt), Britta Engelhardt (Bern), Andreas Reichenbach (Leipzig) and Karen Wolburg-Buchholz, Andreas Mack and Ria Knittel (Tübingen) are gratefully acknowledged.